公开(公告)号：US07923554B2

公开(公告)日：2011-04-12

申请号：US11573224

申请日：2005-08-10

申请人： Georges Joseph Cornelius Hoornaert ,  Amuri Kilonda ,  Jan Heeres ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Lucien Maria Henricus Koymans ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts, legal representative

发明人： Georges Joseph Cornelius Hoornaert ,  Amuri Kilonda ,  Jan Heeres ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Lucien Maria Henricus Koymans ,  Paul Adriaan Jan Janssen

IPC分类号： C07D253/07 ,  C07D253/065 ,  A61K31/53 ,  A61P31/18

CPC分类号： C07D253/075

摘要： The present invention relates to HIV replication inhibitors of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein ring A and ring B represent phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl; n and m are 1 to 4; R1 represents hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl; R2 or R4 represents hydrogen; hydroxy; halo; optionally substituted C1-6alkyl; optionally substituted C2-6alkenyl; optionally substituted C2-6alkynyl; C3-7cycloalkyl; C1-6alkyloxy; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-4alkyl; polyhaloC1-4alkyloxy; polyhaloC1-4alkylthio; —S(═O)pR6; —NH—S(═O)pR6; —C(═O)R6; —NHC(═O)H; —C(═O)NHNH2; NHC(═O)R6; C(═NH)R6; or R7; R2a or R3 represents cyano; aminocarbonyl; amino; halo; NHR13; NR13R14; —C(═O)—NHR13; —C(═O)—NR13R14; —C(═O)—R15; —CH═N—NH—C(═O)—R16; optionally substituted C1-6alkyl; optionally substituted C1-6alkyloxy; optionally substituted C1-6alkyloxyC1-6alkyl; optionally substituted C2-6alkenyl; optionally substituted C2-6alkynyl; —C(═N—O—R8)—C1-4alkyl; R7 or —X3—R7; X1 or X2 represents —NR1—; —NH—NH—; —N═N—; —O—; —C(═O)—; —C1-4alkanediyl-; —CHOH—; —S—; —S(═O)p—; —X4—C1-4alkanediyl-; —C1-4alkanediyl-X4—; or —C1-4alkanediyl-X4—C1-4alkanediyl-; their use as a medicine, their use for the manufacture of a medicament for the treatment or the prevention of HIV infection; their processes for preparation and pharmaceutical compositions comprising them.

公开(公告)号：US08026245B2

公开(公告)日：2011-09-27

申请号：US10573364

申请日：2004-09-21

申请人： Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts, legal representative ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Hendrik Maarten Vinkers ,  Ruben Gerardus George Leenders ,  Dirk Alfons Leo Vandenput

发明人： Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Hendrik Maarten Vinkers ,  Ruben Gerardus George Leenders ,  Dirk Alfons Leo Vandenput

IPC分类号： C07D473/16 ,  C07D473/18 ,  A61K31/52 ,  A61K31/522 ,  A61P31/18 ,  C07D473/40

CPC分类号： A61K31/52 ,  C07D473/00 ,  C07D473/16 ,  C07D473/18

摘要： The present invention relates to the use of a compound of formula (I) for the manufacture of a medicament for the prevention or the treatment of HIV infection wherein the compound of formula (I) is a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein A and B each represents a radical of formula and wherein —C-D- represents a bivalent radical of formula —N═CH—NR17—  (c-1); or —NR17—CH═N—  (c-2); provided that when A represents a radical of formula (a) then B represents a radical of formula (b) and when A represents a radical of formula (b) then B represents a radical of formula (a).

摘要翻译： 本发明涉及式（I）化合物在制备用于预防或治疗HIV感染的药物中的用途，其中式（I）化合物为式I化合物，N-氧化物，药学上 其中A和B各自表示式的基团，其中-CD-表示式-N = CH-NR 17 - （c-1）的二价基团; 或-NR17-CH = N-（c-2）; 条件是当A表示式（a）的基团时，B表示式（b）的基团，并且当A表示式（b）的基团时，B表示式（a）的基团。

公开(公告)号：US08080551B2

公开(公告)日：2011-12-20

申请号：US11474855

申请日：2006-06-26

申请人： Jérôme Emile Georges Guillemont ,  Patrice Palandijian ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts, legal representative

发明人： Jérôme Emile Georges Guillemont ,  Patrice Palandijian ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen

IPC分类号： A61K31/501 ,  A61K31/497 ,  C07D417/12 ,  C07D417/14 ,  C07D417/06 ,  C07D401/12 ,  C07D401/14 ,  C07D401/06 ,  C07D403/12 ,  C07D403/14 ,  C07D403/06 ,  C07D405/12 ,  C07D405/14 ,  C07D405/06 ,  C07D409/14 ,  C07D409/12 ,  C07D409/06 ,  C07D237/20 ,  C07F9/02 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07C257/06 ,  C07C211/40 ,  C07C233/03 ,  C07C235/06 ,  C07C237/20 ,  C07C239/08 ,  C07C229/34 ,  C07C255/49 ,  C07C207/02

CPC分类号： C07D239/48 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07C255/42 ,  C07C257/12 ,  C07D239/47 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： HIV replication inhibitors having formula (I) defined herein are disclosed. Pharmaceutical compositions containing the HIV replication inhibitors; the use of the HIV replication inhibitors in the treatment of HIV; and processes for preparing the HIV replication inhibitors are also disclosed.

摘要翻译： 公开了具有本文定义的式（I）的HIV复制抑制剂。 含有HIV复制抑制剂的药物组合物; 使用HIV复制抑制剂治疗艾滋病毒; 还公开了制备HIV复制抑制剂的方法。

公开(公告)号：US07585861B2

公开(公告)日：2009-09-08

申请号：US10544584

申请日：2004-02-05

申请人： Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Jozef Herwig Arts, legal representative ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Georges Joseph Cornelius Hoomaert ,  Amuri Kilonda ,  Donald William Ludovici

发明人： Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Georges Joseph Cornelius Hoomaert ,  Amuri Kilonda ,  Donald William Ludovici

IPC分类号： C07D253/075 ,  A61K31/53 ,  A61P31/18 ,  C07D403/12 ,  C07D403/14

CPC分类号： A61K31/53 ,  C07D253/07 ,  C07D253/075

摘要： The present invention relates to HIV replication inhibitors of formula (I) as defined in the specification their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及如本说明书中定义的式（I）的HIV复制抑制剂，其用作药物，其制备方法和包含它们的药物组合物。

公开(公告)号：US20120076835A1

公开(公告)日：2012-03-29

申请号：US13249796

申请日：2011-09-30

申请人： Jérôme Emile Georges Guillemont ,  Patrice Palandijian ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts

发明人： Jérôme Emile Georges Guillemont ,  Patrice Palandijian ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts

IPC分类号： A61K9/14 ,  A61K31/505 ,  C07D405/12 ,  A61K31/506 ,  C07D417/12 ,  A61K31/541 ,  C07D401/12 ,  C07D409/12 ,  C07D413/12 ,  A61K31/5377 ,  C07D403/12 ,  A61K31/551 ,  C07D401/14 ,  C07D403/14 ,  C07D239/47 ,  A61P31/18 ,  C07D239/48 ,  B82Y5/00

CPC分类号： C07D239/48 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07C255/42 ,  C07C257/12 ,  C07D239/47 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： This invention concerns HIV replication inhibitors of formula the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及具有N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构形式的式II的HIV复制抑制剂; 它们作为药物的用途，其制备方法和包含它们的药物组合物。

公开(公告)号：US07105522B2

公开(公告)日：2006-09-12

申请号：US10468447

申请日：2002-03-13

申请人： Paul Adriaan Jan Janssen ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Lucien Maria Henricus Koymans ,  Marc René de Jonge ,  Jan Heeres ,  Frederik Frans Desire Daeyaert ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Amuri Kilonda

发明人： Paul Adriaan Jan Janssen ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Lucien Maria Henricus Koymans ,  Marc René de Jonge ,  Jan Heeres ,  Frederik Frans Desire Daeyaert ,  Georges Joseph Cornelius Hoornaert ,  Frans Josef Cornelius Compernolle ,  Amuri Kilonda

IPC分类号： A61K31/4965 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D241/02

CPC分类号： C07D241/20

摘要： This invention concerns a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein R1 is hydrogen, hydroxy, cyano, amino, mono-or di(C1-4alkyl)amino, formyl, carboxyl, C1-6alkyl, hydroxyC1-6alkyl, polyhaloC1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkylcarbonyl, aminocarbonyl, —S(═O)m—NH2, mono-or di(C1-4alkyl)aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy, aryl, arylC1-6alkyl or aryloxy; R2 is hydrogen; halo; mercapto; formyl; cyano; carboxy; azido; hydroxy; oxiranyl; amino; mono- or di(C1-4alkyl)amino; formylamino; R5R6N—C(═O)—; R7—N═C(R8)—; C1-6alkyl-S(═O)m; aryl-S(═O)m; optionally substituted C2-6alkenyl; optionally substituted C2-6alkynyl; C1-6alkyloxy; hydroxyC1-6alkyloxy; aminoC1-6alkyloxy; mono- or di(C1-4alkyl)amino-C1-6alkyloxy; C1-6alkylcarbonyl; arylcarbonyl; Het1carbonyl; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; aryl; aryloxy; arylC1-6alkyloxy; arylthio; arylC1-6alkylthio; mono- or di(aryl)amino; Het1; Het1oxy; Het1thio; Het1C1-6alkyloxy; Het1C1-6alkylthio; mono- or di(Het1)amino; C3-7cycloalkyl; C3-7cycloalkyloxy; C3-7cycloalkylthio; C1-6alkylthio; hydroxyC1-6alkylthio; aminoC1-6alkylthio; mono- or di(C1-4alkyl)aminoC1-6alkylthio; optionally substituted C1-6alkyl; R3 or R4 each independently represent optionally be substituted phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl; —X— is a bivalent radical selected from —NR14—, —NH—NH—, —N═N—, —O—, —C1-6alkanediyl-, —C(═O)—, —CHOH—, —S—, —S(═O)m—; aryl is optionally substituted phenyl; Het1, Het2 or Het3 represent an optionally substituted monocyclic or bicyclic heterocycle; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

公开(公告)号：US20090012092A1

公开(公告)日：2009-01-08

申请号：US11573224

申请日：2005-08-10

申请人： Georges Joseph Cornelius Hoornaert ,  Amuri Kilonda ,  Jan Heeres ,  Paulus Joannes Lewi ,  Marc Rene de Jonge ,  Frederik Frans Desire Daeyaert ,  Hendrik Maarten Vinkers ,  Lucien Maria Henricus Koymans ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts

发明人： Georges Joseph Cornelius Hoornaert ,  Amuri Kilonda ,  Jan Heeres ,  Paulus Joannes Lewi ,  Marc Rene de Jonge ,  Frederik Frans Desire Daeyaert ,  Hendrik Maarten Vinkers ,  Lucien Maria Henricus Koymans ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts

IPC分类号： A61K31/53 ,  C07D253/06 ,  A61P31/18

CPC分类号： C07D253/075

摘要： The present invention relates to HIV replication inhibitors of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein ring A and ring B represent phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl; n and m are 1 to 4; R1 represents hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxyC1-6alkylcarbonyl substituted with C1-6alkyloxycarbonyl; R2 or R4 represents hydrogen; hydroxy; halo; optionally substituted C1-6alkyl; optionally substituted C2-6alkenyl; optionally substituted C2-6alkynyl; C3-7cycloalkyl; C1-6alkyloxy; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-4alkyl; polyhaloC1-4alkyloxy; polyhaloC1-4alkylthio; —S(═O)pR6; —NH—S(═O)pR6; —C(═O)R6; —NHC(═O)H; —C(═O)NHNH2; NHC(═O)R6; C(═NH)R6; or R7; R2a or R3 represents cyano; aminocarbonyl; amino; halo; NHR13; NR13R14 —C(═O)—NHR13; —C(═O)—NR13 R14; —C(═O)—R15; —CH═N—NH—C(═O)—R16; optionally substituted C1-6alkyl; optionally substituted C1-6alkyloxy; optionally substituted C1-6alkyloxyC1-6alkyl; optionally substituted C2-6alkenyl; optionally substituted C2-6alkynyl; —C(═N—O—R8)—C1-4alkyl; R7 or —X3—R7; X1 or X2 represents —NR1—; —NH—NH—; —N═N—; —O—; —C(═O)—; —C1-4alkanediyl-; —CHOH—; —S—; —S(═O)p—; —X4—C1-4alkanediyl-; —C1-4alkanediyl-X4—; or —C1-4alkanediyl-X4—C1-4alkanediyl-; their use as a medicine, their use for the manufacture of a medicament for the treatment or the prevention of HIV infection; their processes for preparation and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及式N-氧化物的HIV复制抑制剂，其药学上可接受的加成盐，季胺或其立体化学异构形式，其中环A和环B表示苯基，吡啶基，哒嗪基，嘧啶基或吡嗪基; n和m为1〜4; R1表示氢; 芳基; 甲酰基 C 1-6烷基羰基; C 1-6烷氧基羰基; 任选取代的C 1-6烷基; 被C 1-6烷氧基羰基取代的C 1-6烷氧基C 1-6烷基羰基; R2或R4代表氢; 羟基; 光环; 任选取代的C 1-6烷基; 任选取代的C 2-6烯基; 任选取代的C 2-6炔基; C 3-7环烷基; C 1-6烷氧基; C 1-6烷氧基羰基; C 1-6烷基羰基氧基; 羧基; 氰基; 硝基 氨基; 单或二（C 1-6烷基）氨基; 多卤代C 1-4烷基; 多卤代1-4烷基氧基; 多卤代 -S（-O）p R 6; -NH-S（-O）p R 6; -C（-O）R 6; -NHC（-O）H; -C（-O）NHNH 2; NHC（-O）R 6; C（-NH）R 6; 或R7; R2a或R3表示氰基; 氨基羰基; 氨基; 光环; NHR13; NR 13 R 14 -C（-O）-NHR 13; -C（ - ） - NR 13 R 14; -C（-O）-R 15; -CH-N-NH-C（-O）-R16; 任选取代的C 1-6烷基; 任选取代的C 1-6烷氧基; 任选取代的C 1-6烷氧基C 1-6烷基; 任选取代的C 2-6烯基; 任选取代的C 2-6炔基; -C（-N-O-R 8）-C 1-4烷基; R7或-X3-R7; X1或X2表示-NR1-; -NH-NH-; -N-N- -O-; -C（-O） - ; -C 1-4烷二基 -CHOH-; -S-; -S（-O）p - ; -X4-C1-4烷二基 -C 1-4烷二基-X4-; 或-C1-4烷二基-X4-C1-4烷二基; 它们作为药物的用途，它们用于制备用于治疗或预防HIV感染的药物的用途; 其制备方法和包含它们的药物组合物。

公开(公告)号：US07442705B2

公开(公告)日：2008-10-28

申请号：US10545358

申请日：2004-02-20

申请人： Jerôme Emile Georges Guillemont ,  Elisabeth Thérese Jeanne Pasquier ,  Jan Heeres ,  Kurt Hertogs ,  Eva Bettens ,  Paulus Joannes Lewi ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Frank Xavier Jozef Herwig, legal representative

发明人： Paul Adriaan Jan Janssen

IPC分类号： C07D239/47 ,  C07D239/48 ,  C07D407/12 ,  A61K31/505 ,  A61P31/18

CPC分类号： C07D239/47 ,  C07D239/48 ,  C07D413/12

摘要： This invention concerns HIV replication inhibitors of formula (I), The N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及式（I）的N-复制抑制剂，N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构形式，它们作为药物的用途，其制备方法和包含它们的药物组合物。

公开(公告)号：US08828982B2

公开(公告)日：2014-09-09

申请号：US12567051

申请日：2009-09-25

申请人： Jan Heeres ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Jéròme Emile Georges Guillemont ,  Elisabeth Therese Jeanne Pasquier ,  Frank Xavier Jozef Herwig Arts

发明人： Jan Heeres ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Jéròme Emile Georges Guillemont ,  Elisabeth Therese Jeanne Pasquier

IPC分类号： A01N43/00 ,  A61K31/33 ,  A61K39/395

CPC分类号： A61K31/513 ,  C07D239/47 ,  C07D239/48 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： This invention concerns the use of a compound for the manufacture of a medicament for the prevention of HIV infection via sexual intercourse and related intimate contact between partners, wherein the compound is a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein the ring containing -a1=a2-a3=a4- and -b1=b2-b3=b4- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy; substituted C1-6alkyloxyC1-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or a 5-membered heterocycle; X1 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, C1-4alkanediyl, —CHOH—, —S—, —S(═O)p—, —X2—C1-4alkanediyl- or —C1-4alkanediyl-X2—; R3 is NHR13; NR13R14; —C(═O)—NHR13; —C(═O)—NR13R14; —C(═O)—R15; —CH═N—NH—C(═O)—R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; —C(═N—O—R8)—C1-4alkyl; R7; or —X3—R7; R4 is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; and pharmaceutical compositions comprising them.

公开(公告)号：US07514445B2

公开(公告)日：2009-04-07

申请号：US10493452

申请日：2002-10-29

申请人： Eddy Jean Edgard Freyne ,  Peter Jacobus Johannes Antonius Buijnsters ,  Marc Willems ,  Werner Constant Johan Embrechts ,  Christopher John Love ,  Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Jan Heeres ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Koen Jeanne Alfons Van Aken ,  Gaston Stanislas Marcella Diels

发明人： Eddy Jean Edgard Freyne ,  Peter Jacobus Johannes Antonius Buijnsters ,  Marc Willems ,  Werner Constant Johan Embrechts ,  Christopher John Love ,  Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Jan Heeres ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Koen Jeanne Alfons Van Aken ,  Gaston Stanislas Marcella Diels

IPC分类号： A61K31/506 ,  A61P3/10 ,  A61P25/28 ,  A61P25/02 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14

CPC分类号： C07D213/74 ,  C07D239/42 ,  C07D239/48 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12

摘要： This invention concerns a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein ring A is a 6-membered heterocycle; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyloxyC1-6alkylcarbonyl; X is a direct bond or a linker atom or group; Z is a direct bond or a linker atom or group; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, a carbocycle or a heterocycle, each of said groups may optionally be substituted; R3 is hydrogen; hydroxy; halo; optionally substituted C1-6alkyl or C2-6alkenyl or C2-6alkynyl; C1-6alkyloxy; C1-6alkylthio; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; polyhaloC1-6alkylthio; R21; R21—C1-6alkyl; R21—O—; R21—S—; R21—C(═O)—; R21—S(═O)p—; R7—S(═O)p—; R7—S(═O)p—NH—; R21—S(═O)p—NH—; R7—C(═O)—; —NHC(═O)H; —C(═O)NHNH2; R7—C(═O)—NH—; R21—C(═O)—NH—; —C(═NH)R7—C(═NH)R21; R4 is an optionally substituted heterocycle provided that —X—R2 and/or R3 is other than hydrogen; their use, pharmaceutical compositions comprising them and processes for their preparation.

摘要翻译： 本发明涉及式的化合物N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构形式，其中环A是6-元杂环; R1是氢; 芳基; 甲酰基 C 1-6烷基羰基; 任选取代的C 1-6烷基; C 1-6烷氧基羰基; 任选取代的C 1-6烷氧基C 1-6烷基羰基; X是直接键或连接原子或基团; Z是直接键或连接原子或基团; R 2是氢，C 1-10烷基，C 2-10烯基，C 2-10炔基，碳环或杂环，所述基团中的每一个可任选被取代; R3是氢; 羟基; 光环; 任选取代的C 1-6烷基或C 2-6烯基或C 2-6炔基; C 1-6烷氧基; C 1-6烷硫基; C 1-6烷氧基羰基; C 1-6烷基羰基氧基; 羧基; 氰基; 硝基 氨基; 单或二（C 1-6烷基）氨基; 多卤代C 1-6烷基; 多卤代C 1-6烷氧基; 多卤代C 1-6烷硫基; R21; R21-C1-6烷基; R21-O-; R21-S-; R21-C（-O） - ; R21-S（-O）p-; R7-S（-O）p-; R7-S（-O）p-NH-; R21-S（-O）p-NH-; R7-C（-O） - ; -NHC（-O）H; -C（-O）NHNH 2; R7-C（-O）-NH-; R 21 -C（-O）-NH-; -C（ - NH）R 7 -C（-NH）R 21; R4是任选取代的杂环，条件是-X-R 2和/或R 3不是氢; 其用途，包含它们的药物组合物及其制备方法。